MACTFusion: Lightweight Cross Transformer for Adaptive Multimodal Medical Image Fusion.

Multimodal medical image fusion aims to integrate complementary information from different modalities of medical images. Deep learning methods, especially recent vision Transformers, have effectively improved image fusion performance. However, there are limitations for Transformers in image fusion, such as lacks of local feature extraction and cross-modal feature interaction, resulting in insufficient multimodal feature extraction and integration. In addition, the computational cost of Transformers is higher. To address these challenges, in this work, we develop an adaptive cross-modal fusion strategy for unsupervised multimodal medical image fusion. Specifically, we propose a novel lightweight cross Transformer based on cross multi-axis attention mechanism. It includes cross-window attention and cross-grid attention to mine and integrate both local and global interactions of multimodal features. The cross Transformer is further guided by a spatial adaptation fusion module, which allows the model to focus on the most relevant information. Moreover, we design a special feature extraction module that combines multiple gradient residual dense convolutional and Transformer layers to obtain local features from coarse to fine and capture global features. The proposed strategy significantly boosts the fusion performance while minimizing computational costs. Extensive experiments, including clinical brain tumor image fusion, have shown that our model can achieve clearer texture details and better visual quality than other state-of-the-art fusion methods.

Lipid-lowering drugs and inflammatory bowel disease's risk: a drug-target Mendelian randomization study.

BACKGROUND: Inflammatory bowel disease (IBD) has been associated with lipid-lowering drugs in observational studies. Drug-target Mendelian randomization (MR) was utilized in this study to examine the causal relationship between lipid-lowering drugs and incidence of IBD, aiming to identify new preventive uses for the drugs. METHODS: We identified instrumental variables for three classes of lipid-lowering drugs: HMGCR inhibitors, PCSK9 inhibitors, and NPC1L1 inhibitors, using data from the Global Lipids Genetics Consortium. Summary statistics of IBD were obtained from UK Inflammatory Bowel Disease Genetics. The summary-data-based MR (SMR) and the inverse-variance weighted (IVW) MR were used for analysis. Sensitivity analyses were performed by conventional MR methods. RESULTS: The SMR analysis showed no significant genetic association between increased gene expression of HMGCR, PCSK9, and NPC1L1 and IBD, Crohn's disease (CD) and ulcerative colitis (UC). According to IVW-MR analysis, increased HMGCR expression is associated with a reduced risk of IBD (OR = 0.73, 95% confidence interval (CI) 0.59-0.90, P = 0.003) and CD (OR = 0.75, 95% CI 0.57-0.97, P = 0.03), but not with UC. Additionally, increased NPC1L1 gene expression was associated with elevated risk of IBD (OR = 1.60, 95% CI 1.07-2.40, P = 0.023), but not with CD and UC. However, no significant causal relationships were found between PCSK9 gene expression and IBD, CD, and UC. The sensitivity analysis demonstrated no evidence of heterogeneity or pleiotropy among the reported results. CONCLUSIONS: The heightened expression of genetic variations in HMGCR inhibitor targets could potentially reduce the risk of IBD and CD, while genetic variation in the expression of NPC1L1 targets was positively associated with IBD.

A bistable autoregulatory module in the developing embryo commits cells to binary expression fates.

Bistable autoactivation has been proposed as a mechanism for cells to adopt binary fates during embryonic development. However, it is unclear whether the autoactivating modules found within developmental gene regulatory networks are bistable, unless their parameters are quantitatively determined. Here, we combine in vivo live imaging with mathematical modeling to dissect the binary cell fate dynamics of the fruit fly pair-rule gene fushi tarazu (ftz), which is regulated by two known enhancers: the early (non-autoregulating) element and the autoregulatory element. Live imaging of transcription and protein concentration in the blastoderm revealed that binary Ftz fates are achieved as Ftz expression rapidly transitions from being dictated by the early element to the autoregulatory element. Moreover, we discovered that Ftz concentration alone is insufficient to activate the autoregulatory element, and that this element only becomes responsive to Ftz at a prescribed developmental time. Based on these observations, we developed a dynamical systems model and quantitated its kinetic parameters directly from experimental measurements. Our model demonstrated that the ftz autoregulatory module is indeed bistable and that the early element transiently establishes the content of the binary cell fate decision to which the autoregulatory module then commits. Further in silico analysis revealed that the autoregulatory element locks the Ftz fate quickly, within 35 min of exposure to the transient signal of the early element. Overall, our work confirms the widely held hypothesis that autoregulation can establish developmental fates through bistability and, most importantly, provides a framework for the quantitative dissection of cellular decision-making.

Causal associations between inflammatory bowel disease and primary biliary cholangitis: a two-sample bidirectional Mendelian randomization study.

Inflammatory bowel disease (IBD) has been reported to be associated with hepatobiliary diseases. Previous observational and Mendelian randomization (MR) studies have suggested a causal association between IBD and primary sclerosing cholangitis (PSC). However, it is unclear whether IBD has a causal association with primary biliary cholangitis (PBC): another autoimmune liver disease. We obtained genome-wide association study (GWAS) statistics from published GWASs for PBC, UC, and CD. We screened qualified instrumental variables (IVs) based on the three major assumptions of MR. To determine the causal relationships between UC or CD and PBC, two-sample MR analyses were performed using inverse variance-weighted (IVW), MR-Egger, and weighted median (WM) methods, and sensitivity analyses were conducted to validate the robustness of the results. We also conducted reverse MR analysis to reveal the causal association between PBC and UC or CD. UC was associated with a higher risk of PBC (OR 1.35, 95% CI 1.05-1.73, P = 0.02) in the IVW method, and CD was associated with an increased risk of PBC (OR 1.18, 95% CI 1.03-1.36, P = 0.02) in IVW. The weighted median and MR-Egger regression of both diseases showed a consistent direction but were not statistically significant. Results of the reverse MR analysis did not suggest genetic susceptibility that PBC was associated with an increased risk of UC (OR 1.05, 95% CI 0.95-1.17, P = 0.34) or CD (OR 1.1, 95% CI 0.99-1.20, P = 0.06). The present study revealed that IBD subtypes could increase the incidence of PBC, but in turn, PBC did not increase the incidence of IBD subtypes. Understanding that IBD and PBC constitute mutual risk factors can help with the clinical management of both diseases.

Quantitative phase imaging of living red blood cells combining digital holographic microscopy and deep learning.

Digital holographic microscopy as a non-contacting, non-invasive, and highly accurate measurement technology, is becoming a valuable method for quantitatively investigating cells and tissues. Reconstruction of phases from a digital hologram is a key step in quantitative phase imaging for biological and biomedical research. This study proposes a two-stage deep convolutional neural network named VY-Net, to realize the effective and robust phase reconstruction of living red blood cells. The VY-Net can obtain the phase information of an object directly from a single-shot off-axis digital hologram. We also propose two new indices to evaluate the reconstructed phases. In experiments, the mean of the structural similarity index of reconstructed phases can reach 0.9309, and the mean of the accuracy of reconstructions of reconstructed phases is as high as 91.54%. An unseen phase map of a living human white blood cell is successfully reconstructed by the trained VY-Net, demonstrating its strong generality.

Investigating association between gut microbiota and sarcopenia-related traits: a Mendelian randomization study.

Background: Observational studies have indicated a potential link between gut microbiota and sarcopenia. However, the underlying mechanisms and a causal relationship have not been established. Thus, the objective of this study is to examine the possible causal association between gut microbiota and sarcopenia-related traits, including low hand-grip strength and appendicular lean mass (ALM), to shed light on the gut-muscle axis. Methods: To investigate the potential impact of gut microbiota on low hand-grip strength and ALM, we utilized a two-sample Mendelian randomization (MR) approach. Summary statistics were obtained from genome-wide association studies of gut microbiota, low hand-grip strength, and ALM. The primary MR analysis employed the random-effects inverse-variance weighted (IVW) method. To assess the robustness, we conducted sensitivity analyses using the MR pleiotropy residual sum and outlier (MR-PRESSO) test to detect and correct for horizontal pleiotropy, as well as the MR-Egger intercept test and leave-one-out analysis. Results: Alcaligenaceae, Family XIII, and Paraprevotella were positively associated with the risk of low hand-grip strength (P-values < 0.05). Streptococcaceae were negatively associated with low hand-grip strength (P-values < 0.05). Eight bacterial taxa (Actinomycetales, Actinomycetaceae, Bacteroidaceae, Porphyromonadaceae, Prevotellaceae, Bacteroides, Marvinbryantia, and Phascolarctobacterium) were associated with a higher risk of ALM (P-values < 0.05). Eubacterium fissicatena group was negatively associated with ALM (P-values < 0.05). Conclusion: We found several gut microbiota components causally associated with sarcopenia-related traits. Our findings provided insights into novel strategies for the prevention and treatment of sarcopenia through the regulation of the gut microbiota, contributing to a better understanding of the gut-muscle axis.

Synchronous Phase-Shifting Interference for High Precision Phase Imaging of Objects Using Common Optics.

Quantitative phase imaging and measurement of surface topography and fluid dynamics for objects, especially for moving objects, is critical in various fields. Although effective, existing synchronous phase-shifting methods may introduce additional phase changes in the light field due to differences in optical paths or need specific optics to implement synchronous phase-shifting, such as the beamsplitter with additional anti-reflective coating and a micro-polarizer array. Therefore, we propose a synchronous phase-shifting method based on the Mach-Zehnder interferometer to tackle these issues in existing methods. The proposed method uses common optics to simultaneously acquire four phase-shifted digital holograms with equal optical paths for object and reference waves. Therefore, it can be used to reconstruct the phase distribution of static and dynamic objects with high precision and high resolution. In the experiment, the theoretical resolution of the proposed system was 1.064 µm while the actual resolution could achieve 1.381 µm, which was confirmed by measuring a phase-only resolution chart. Besides, the dynamic phase imaging of a moving standard object was completed to verify the proposed system's effectiveness. The experimental results show that our proposed method is suitable and promising in dynamic phase imaging and measurement of moving objects using phase-shifting digital holography.

Sleep traits and risk of end-stage renal disease: a mendelian randomization study.

BACKGROUND: Epidemiological evidence relating sleep disorders to end-stage renal disease (ESRD) has been obscure. The present study is sought to examine the association between sleep traits and ESRD. METHODS: For this analysis, we selected genetic instruments for sleep traits from published genome-wide association studies (GWAS). As instrumental variables, independent genetic variations linked with seven sleep-related features (sleep duration, getting up in the morning, daytime napping, chronotype of morning/evening person, sleeplessness/insomnia, non-snoring, and daytime dozing) were chosen. A two-sample Mendelian randomization (TSMR) study was conducted to assess the causal relationship between sleep traits and ESRD (N = 33,061). The reverse MR analysis subsequently determined the causal relationship between ESRD and sleep traits. The causal effects were estimated using inverse variance weighted, MR-Egger, weighted median. To conduct sensitivity studies, Cochran's Q test, MR-Egger intercept test, MR-PRESSO, leave-one-out analysis, and funnel plot were used. To study the potential mediators, multivariable mendelian randomization analyses were undertaken further. RESULTS: Genetically predicted sleeplessness/ insomnia (OR = 6.11, 95%CI 1.00-37.3, P = 0.049, FDR = 0.105), getting up in the morning easily(OR = 0.23, 95%CI 0.063-0.85; P = 0.0278, FDR = 0.105), non-snoring (OR = 4.76E-02, 95%CI 2.29E-03-0.985, P = 0.0488, FDR = 0.105) was suggestively associated with the risk of ESRD. However, we found no evidence favoring a causal association between other sleep traits and ESRD through the IVW method. CONCLUSION: The present TSMR found no strong evidence of a bidirectional causal association between genetically predicted sleep traits and ESRD.

Probabilistic risk analysis of unit trains versus manifest trains for transporting hazardous materials.

When transporting hazardous materials by rail, train types (unit train or manifest train) can influence derailment and release risks in several ways. Unit trains only experience risks on mainlines and when arriving at or departing from terminals, while manifest trains experience additional switching risks in yards. A comprehensive risk assessment methodology is needed to quantitively compare shipments with unit trains and manifest trains, considering both mainline and yard operations. To fulfill this research gap, this paper constructs event chains for line-haul risks, arrival/departure risks, and yard switching risks using various probabilistic models and finally determines expected casualties as the consequences of a potential train derailment and release incident. Five illustrative scenarios are designed to analyze the best and worst cases and compare the transportation risk differences between service options using unit trains and manifest trains. The comparison results indicate that placing all tank cars at the positions with the lowest probability of derailing and switching tank cars alone in classification yards could provide the lowest risk estimate given the same transportation demand.

Minimal synthetic enhancers reveal control of the probability of transcriptional engagement and its timing by a morphogen gradient.

How enhancers interpret morphogen gradients to generate gene expression patterns is a central question in developmental biology. Recent studies have proposed that enhancers can dictate whether, when, and at what rate promoters engage in transcription, but the complexity of endogenous enhancers calls for theoretical models with too many free parameters to quantitatively dissect these regulatory strategies. To overcome this limitation, we established a minimal promoter-proximal synthetic enhancer in embryos of Drosophila melanogaster. Here, a gradient of the Dorsal activator is read by a single Dorsal DNA binding site. Using live imaging to quantify transcriptional activity, we found that a single binding site can regulate whether promoters engage in transcription in a concentration-dependent manner. By modulating the binding-site affinity, we determined that a gene's decision to transcribe and its transcriptional onset time can be explained by a simple model where the promoter traverses multiple kinetic barriers before transcription can ensue.

Working status and risk of Alzheimer's disease: A Mendelian randomization study.

BACKGROUND: Alzheimer's disease (AD) has become a common illness affecting the elderly, adding to society's social and financial burden. We used two-sample Mendelian randomization (MR) in this study to determine the association between working status and AD. METHODS: We performed a two-sample MR analysis. The genetic associations were derived from the UK Biobank (n = 263,615) and the International Genomics of Alzheimer's Project (n = 63,926). Inverse variance weighted (IVW), MR-Egger, and weighted median were used in the MR analysis. The funnel plot, Cochran's Q test, MR-Egger intercept test, and leave-one-out analysis were used in sensitivity analyses. Further risk factor analyses were carried out to look into the potential mediators. RESULTS: Jobs involve heavy manual or physical work (OR = 2.13, 95%CI 1.36-3.36; p = .0011), job involves mainly walking or standing (OR = 1.74, 95%CI 1.19-2.54; p = .004), and job involves shift work (OR = 2.78, 95%CI 1.14-6.80; p = .02) increased the risk of AD in the IVW analysis. There was no heterogeneity and no horizontal pleiotropy in the sensitivity analysis. Risk factor analysis suggested that each of the above association may be mediated by different risk factors. CONCLUSION: Our study adds to the evidence that the development of AD is associated with the working status (job involves heavy manual or physical work, job involves mainly walking or standing, and job involves shift work) by using extensive human genetic data.

Medication Regimen Complexity and Risk of Bleeding in People Who Initiate Oral Anticoagulants for Atrial Fibrillation: A Population-Based Study.

BACKGROUND: Oral anticoagulants (OACs) are high-risk medications often used in older people with complex medication regimens. This study was the first to assess the association between overall regimen complexity and bleeding in people with atrial fibrillation (AF) initiating OACs. METHODS: Patients diagnosed with AF who initiated an OAC (warfarin, dabigatran, rivaroxaban, apixaban) between 2010 and 2016 were identified from the Hong Kong Clinical Database and Reporting System. Each patient's Medication Regimen Complexity Index (MRCI) score was computed. Baseline characteristics were balanced using inverse probability of treatment weighting. People were followed until a first hospitalization for bleeding (intracranial hemorrhage, gastrointestinal bleeding, or other bleeding) and censored at discontinuation of the index OAC, death, or end of the follow-up period, whichever occurred first. Cox regression was used to estimate hazard ratios (HR) between MRCI quartiles and bleeding during initiation and all follow-up. RESULTS: There were 19 292 OAC initiators (n = 9 092 warfarin, n = 10 200 direct oral anticoagulants) with a mean (standard deviation) age at initiation of 73.9 (11.0) years. More complex medication regimens were associated with an increased risk of bleeding (MRCI > 14.0-22.00: aHR 1.17, 95% confidence interval [CI] 0.93-1.49; MRCI > 22.0-32.5: aHR 1.32, 95%CI 1.06-1.66; MRCI > 32.5: aHR 1.45, 95%CI 1.13-1.87, compared to MRCI ≤ 14). No significant association between MRCI and bleeding risk was observed during the initial 30, 60, or 90 days of treatment. CONCLUSION: In this cohort study of people with AF initiating an OAC, a more complex medication regimen was associated with higher bleeding risk over periods longer than 90 days. Further prospective studies are needed to assess whether MRCI should be considered in OAC prescribing.

VDE-Net: a two-stage deep learning method for phase unwrapping.

Phase unwrapping is a critical step to obtaining a continuous phase distribution in optical phase measurements and coherent imaging techniques. Traditional phase-unwrapping methods are generally low performance due to significant noise or undersampling. This paper proposes a deep convolutional neural network (DCNN) with a weighted jump-edge attention mechanism, namely, VDE-Net, to realize effective and robust phase unwrapping. Experimental results revealed that the weighted jump-edge attention mechanism, which is first proposed and simple to calculate, is useful for phase unwrapping. The proposed algorithm outperformed other networks or common attention mechanisms. In addition, an unseen wrapped phase image of a living red blood cell (RBC) was successfully unwrapped by the trained VDE-Net, thereby demonstrating its strong generalization capability.

Effects of nutritional supplement and resistance training for sarcopenia in patients with inflammatory bowel disease: A randomized controlled trial.

BACKGROUND: Nutritional supplementation and resistance training are broadly recommended as part of the treatment of sarcopenia, but studies that have evaluated interventions in inflammatory bowel disease patients with sarcopenia are lacking. The aim of this study was to evaluate the effects of nutritional supplementation and resistance training for improving height-adjusted appendicular skeletal muscle mass (ASM/H2) and medical indices in patients with inflammatory bowel disease. METHODS: This randomized, double-blind, placebo-controlled trial of forty-five participants was performed at Huadong Hospital Affiliated to Fudan University in Shanghai from September 2020 to June 2021. Eligible participants were randomly assigned to receive whey protein (10 g/d) or placebo (10 g/d) for 8 weeks while completing a resistance training program (3 times a week). Data such as ASM/H2 and other medical indices were collected at baseline and at 4 and 8 weeks of intervention. RESULTS: Fifteen participants were allocated to the resistance training and whey protein (RT+WP) group, and thirteen participants were allocated to the resistance training and placebo (RT+placebo) group. The ASM/H2 significantly increased in the RT+WP group after 4 and 8 weeks of intervention, and the ASM/H2 of the RT+WP group was significantly higher than that of the RT+placebo group after 4 and 8 weeks of intervention (F = 1.092, P = .035). Both interventions significantly increased albumin (F = 7.214, P = .003). Hemoglobin and creatinine significantly increased in the RT+WP group (F = 3.592, P = .035; F = 3.922, P = .033, respectively). In addition, a significant group × time interaction was not observed for body mass index, 5-time chair stand test time, 3-metre walk speed, grip strength, waist circumference, hip circumference, or waist-to-hip ratio (P > .05). CONCLUSIONS: Nutritional supplementation may be effective in improving sarcopenia, as well as many other physiological indicators during resistance training.

Caffeine intake and the risk of incident kidney stones: a systematic review and meta-analysis.

BACKGROUND: Kidney stone disease is increasingly common in the general population, with a high recurrence rate after stone removal. It has been proven that caffeine consumption can reduce the risk of diseases, such as stroke and dementia. However, the effect of caffeine intake on the incidence of kidney stones has not been determined. This systematic review and meta-analysis were performed to evaluate the association of caffeine intake with the risk of incident kidney stones. METHODS: PubMed, Web of Science, Scopus, Cochrane and Google Scholar were searched using terms related to coffee, caffeine and kidney stones to find eligible articles up to December 2021. Articles with clear diagnostic criteria for kidney stone disease and the exact intake dose of caffeine were included. The incidence of kidney stone disease was the main outcome. Summarized risk estimates and 95% CIs for the highest and lowest categories of caffeine intake were calculated using a random effects model. RESULTS: Seven studies were included in the final meta-analysis, with 9707 cases of kidney stones and a total of 772,290 cohort members. Compared with the lowest category of caffeine intake, the pooled relative risk (RR) was 0.68 ([95% CI 0.61-0.75], I2 = 57%) for the highest category of caffeine intake. Subgroup analyses showed that caffeine intake had an inverse relationship with the incidence of kidney stones in all subgroups. CONCLUSION: This study suggests that a higher caffeine intake may be associated with a lower risk of incident kidney stones.

COVID-19 Vaccination Preferences of University Students and Staff in Hong Kong.

Importance: COVID-19 has required universities to rapidly develop vaccination policies for students and staff, yet little is known about the preferences of these individuals toward vaccination. Objective: To quantify student and staff preferences for COVID-19 vaccination at a university in Hong Kong. Design, Setting, and Participants: A cross-sectional online survey study was conducted from July 20 to September 21, 2021, before the announcement of a campus-wide vaccine mandate. A survey of 42 451 eligible university students and staff used discrete-choice experiment methods to quantify 7 attributes of COVID-19 vaccination: risk of a mild or moderate adverse event after vaccination, risk of a severe adverse event after vaccination, efficacy against COVID-19 infection, efficacy against severe manifestation of COVID-19 infection, duration of protection after vaccination, incentive for completing vaccination, and out-of-pocket costs. Main Outcomes and Measures: A mixed logit regression model was used to estimate the preferences of attributes for COVID-19 vaccines and marginal willingness to pay (mWTP) adjusted for background characteristics, role, vaccination, and COVID-19 infection status of family or friends, adverse event status after vaccination among family and friends of participants, and scenario block. Results: Among 42 451 eligible university students and staff invited, 3423 individuals completed the survey (mean [SD] age, 27.1 [9.9] years; 2053 [60.0%] women). Participants included 2506 students (73.2%) and 917 staff (26.8%), with a response rate of 8.1%. Quarantine-free travel was preferred (ß = 0.86; 95% CI, 0.72-0.99; mWTP: $235.9; 95% CI, $190.3-$294.2), followed by efficacy against any COVID-19 infection (ß = 0.30; 95% CI, 0.29-0.32; mWTP: $84.1; 95% CI, $71.8-$100.8), against severe manifestation of COVID-19 infection (ß = 0.25; 95% CI, 0.24-0.27; mWTP: $69.7; 95% CI, $465-$653), and risk of severe adverse events following vaccination (ß = -0.24; 95% CI, -0.27 to -0.21; mWTP: -$66.8; 95% CI, -$81.5 to -$55.3). Participants were less concerned about protection duration (ß = 0.17; 95% CI, 0.15-0.18; mWTP: $46.0; 95% CI, $38.6-$56.2) and risk of mild to moderate adverse events (ß = -0.12; 95% CI, -0.13 to -0.10; mWTP: -$32.7; 95% CI, -$41.2 to -$26.4). Conclusions and Relevance: Preference of all attributes were significant and were considered important by the participants for vaccine decision-making. Insights drawn could assist policy makers in future vaccination decisions, such as campus vaccine mandate and requirement of a third dose.

Safety and effectiveness of low-dose aspirin for the prevention of gastrointestinal cancer in adults without atherosclerotic cardiovascular disease: a population-based cohort study.

OBJECTIVE: To assess the association between low-dose aspirin and the incidence of colorectal cancer (CRC), gastric cancer (GC), oesophageal cancer (EC) and gastrointestinal bleeding (GIB) in adults without established atherosclerotic cardiovascular disease. DESIGN: Cohort study with propensity score matching of new-users of aspirin to non-users. SETTING: Clinical Data Analysis and Reporting System database, Hong Kong. PARTICIPANTS: Adults ≥40 years with a prescription start date of either low-dose aspirin (75-300 mg/daily) or paracetamol (non-aspirin users) between 1 January 2004 to 31 December 2008 without a history of atherosclerotic cardiovascular disease. MAIN OUTCOME MEASURES: The primary outcome was the first diagnosis of gastrointestinal cancer (either CRC, GC or EC) and the secondary outcome was GIB. Individuals were followed from index date of prescription until the earliest occurrence of an outcome of interest, an incident diagnosis of any type of cancer besides the outcome, death or until 31 December 2017. A competing risk survival analysis was used to estimate HRs and 95% CIs with death as the competing risk. RESULTS: After matching, 49 679 aspirin and non-aspirin users were included. The median (IQR) follow-up was 10.0 (6.4) years. HRs for low-dose aspirin compared with non-aspirin users were 0.83 for CRC (95% CI, 0.76 to 0.91), 0.77 for GC (95% CI, 0.65 to 0.92) and 0.88 for EC (95% CI, 0.67 to 1.16). Patients prescribed low-dose aspirin had an increased risk of GIB (HR 1.15, 95% CI, 1.11 to 1.20), except for patients prescribed proton pump inhibitors or histamine H2-receptor antagonists (HR 1.03, 95% CI, 0.96 to 1.10). CONCLUSION: In this cohort study of Chinese adults, patients prescribed low-dose aspirin had reduced risks of CRC and GC and an increased risk of GIB. Among the subgroup of patients prescribed gastroprotective agents at baseline, however, the association with GIB was attenuated.

LibINVENT: Reaction-based Generative Scaffold Decoration for in Silico Library Design.

Because of the strong relationship between the desired molecular activity and its structural core, the screening of focused, core-sharing chemical libraries is a key step in lead optimization. Despite the plethora of current research focused on in silico methods for molecule generation, to our knowledge, no tool capable of designing such libraries has been proposed. In this work, we present a novel tool for de novo drug design called LibINVENT. It is capable of rapidly proposing chemical libraries of compounds sharing the same core while maximizing a range of desirable properties. To further help the process of designing focused libraries, the user can list specific chemical reactions that can be used for the library creation. LibINVENT is therefore a flexible tool for generating virtual chemical libraries for lead optimization in a broad range of scenarios. Additionally, the shared core ensures that the compounds in the library are similar, possess desirable properties, and can also be synthesized under the same or similar conditions. The LibINVENT code is freely available in our public repository at https://github.com/MolecularAI/Lib-INVENT. The code necessary for data preprocessing is further available at: https://github.com/MolecularAI/Lib-INVENT-dataset.

SDoF-Net: Super Depth of Field Network for Cell Detection in Leucorrhea Micrograph.

Accompanied with the rapid increase of the demand for routine examination of leucorrhea, efficiency and accuracy become the primary task. However, in super depth of field (SDoF) system, the problem of automatic detection and localization of cells in leucorrhea micro-images is still a big challenge. The changing of the relative position between the cell center and focus plane of microscope lead to variable cell morphological structure in the two-dimensional image, which is an important reason for the low accuracy of current deep learning target detection algorithms. In this paper, an object detection method based on Retinanet in state of super depth of field is proposed, which can achieve high precision detecting of leucorrhea components by the SDoF feature aggregation module. Compared with the current mainstream algorithms, the mean average accuracy (mAP) index has been improved significantly, the mAP index is 82.7% for SDoF module and 83.0% for SDoF+ module, with an average increase of more than 10%. These improved features can significantly improve the efficiency and accuracy of the algorithm. The algorithm proposed in this paper can be integrated into the leucorrhea automatic detection system.

Relation of substance use disorders to mortality, accident and emergency department attendances, and hospital admissions: A 13-year population-based cohort study in Hong Kong.

BACKGROUND: The impact of substance use disorders (SUD) in an Asian population has not been fully explored. We aimed to assess the risk of mortality, accident and emergency (A&E) department attendances, and hospital admissions associated with SUD in a population-based cohort study. METHOD: Patients diagnosed with SUD in public A&E departments from 2004 to 2016 (N = 8,423) were identified in the Clinical Database Analysis and Reporting System of the Hong Kong Hospital Authority and 1:1 matched to patients without SUD by propensity score (N = 6,074 in each group). Relative risks of mortality, A&E attendances and hospital admissions were assessed using Cox regression and Hurdle negative binomial regression. RESULTS: Patients with SUD had higher mortality (hazard ratio=1.43; 95% confidence interval [CI]=1.26-1.62) and more often died from poisoning or toxicity and injuries. The odds ratio (OR) for A&E attendances and all-cause hospital admissions associated with SUD were 2.80 (95% CI=2.58-3.04) and 3.54 (95% CI=3.26-3.83), respectively. The impact of SUD on the above outcomes was greatest among school-aged individuals (≤ 21 years) and decreased with age. The relative risk of mental disorder-related hospital admissions was much higher than that for infections, respiratory diseases, and cardiovascular diseases. In patients with SUD, ketamine and amphetamine use were associated with increased A&E attendances than opioid use. CONCLUSIONS: SUD was associated with increased mortality, A&E attendances and hospital admissions, especially in school-aged individuals. Our findings suggest prioritising early treatment and preventive interventions for school-aged individuals and focusing on the management of comorbid mental disorders and the use of ketamine and amphetamine.